The present invention relates to active delivery devices and related procedures.
More particularly the invention relates to devices or inserts (hereafter xe2x80x9cdevicesxe2x80x9d) capable of delivering a substance from the device into a surrounding environment whatever that may be. Such delivery will be as a fluid from a storage reservoir for such fluid or its precursor.
Unlike passive diffusion devices of this type the present invention is directed to a device which can achieve an active expression of the fluid from a storage reservoir for such fluid or its precursor and preferably with control of the continuous or intermittent reduction of the volume of the reservoir which achieves the active expression and preferably with a low passive release incidence to any active release incidence and also preferably with a low passive release incidence during any period of no active release.
The environment of any such release may vary.
Such environments include body cavities, plant beds, loci of pest movement, liquid surrounds (eg fish tanks), etc.
The reason for the preferred characteristics will now be described by reference to non-restrictive examples of such use.
As a first example the invention may relate to active delivery devices locatable in a body cavity of an animal to actively release a substance (eg. useful by intra-vagina insertion of synchronising the oestrus of animal or by intraruminal delivery of releasing desired agents into a ruminant).
When one considers the mating of animals, it is useful for farmers to synchronise the oestrus of animals whether they be cattle beasts (whether for dairy or beef purposes) sheep, goats, horses, or the like where artificial insemination is practised. By way of example, in relation to cattle beasts, in a normal 365 day year 282 days on average is taken up of the year with the gestation period itself. With approximately 30 days to recover after delivery of its progeny each cow therefore has an average of only two and a half cycles if there is to be a timely management of the herd. Thus it is important over that remaining period of less than 53 days to ensure each cow in a herd becomes pregnant.
The traditional method of mating dairy cows with bulls is now largely superseded by the use of artificial insemination procedures which offers the prospect of rapid herd improvements although bulls are still presented to the herd frequently to catch those animals that have not conceived by the artificial insemination procedure should they comes into oestrus within a designated time.
There is therefore a great advantage attached to bringing such herd animals into oestrus simultaneously so as to make it easier to ensure effective usage of the artificial insemination procedure and subsequently to enable still within the xe2x80x9cwindowxe2x80x9d a further prospect of artificial insemination of those animals synchronistically brought to oestrus that have not already conceived.
Various means of achieving such a management of the synchronisation of the coming into oestrus of cows (whether heifers or lactating cows) and even sheep and goats has been disclosed in the art which includes the livestock improvement publication of this company (1995 edition) made available to interested parties by this company trading as INTERAG(trademark) in respect of its intra vaginal Eazi-Breed(trademark) CIDR(copyright) product line.
The disclosures in the aforementioned publication, the full contents of which are here included by way of reference, ensures to date the best procedure applicable (at least to New Zealand herds) of cattle beasts to ensure a timely conception of a herd without a significant downgrading of the fecundity of the herd.
As used herein the term xe2x80x9csynchronisexe2x80x9d or the derivatives thereof in respect of the onset of oestrus of an animal is not restricted to exact synchrony but rather relates to a period of time usually measured in days over which the synchrony occurs.
Initial attempts using intra vaginal devices from which progesterone could be leached simply had the effect of preventing oestrus until after they were withdrawn thereby deriving some synchrony in the onset of oestrus thereafter during a period when a heifer or lactating cow is able to cycle. This lead to a three day spread in the synchrony after a 12 to 15 day insertion of the intra vaginal progesterone containing device.
Subsequent efforts to confine the period of the synchrony lead to such a progesterone containing intra vaginal device being inserted shortly after, simultaneously with or shortly before the administration (usually intra vaginally) of an oestradiol. For instance the use of a CIDR(copyright) intra vaginal device as referred to the aforementioned publication simultaneously with a capsule containing ten milligrams of oestradiol and the retention of the CIDR(copyright) intra vaginal device in the animal for ten days led shortly thereafter to a three day synchrony onset of oestrus period.
More recently that last mentioned procedure has been refined for heifers to provide a two day period of synchrony with an 80% of the herd onset of oestrus within the first day. In this refined procedure at about day 6 of the 10 day insertion period a prostaglandin is injected.
The aforementioned procedures are now described in the art. Also described in the art are insemination procedures. It is also known to use substantial repeats of the procedure within the available cycling period referred to so that there is at least one additional prospect of conception by artificial breeding within an appropriate economic window.
With all such procedures however the longer the period of the presence of the progesterone containing intra vaginal device in an animal (about 15 days is the optimum for tightness of the synchronisation) there is a corresponding diminishment in the fertility of individual animals in the herd owing to the effect over time on the follicle development to the fertilisable egg stage. The use of the oestradiol changes follicle growth pattern. Hence with its use an optimisation of the fecundity prospects for the herd can be achieved by better balancing the tightness of the synchronisation (with longer insertion) against the loss of fertility (with longer insertion).
A cost factor arises in the adoption of such procedures as a farmer is faced with the costs of the intra vaginal progesterone containing device as well as the use of the oestradiol and/or prostaglandin materials additionally used. This ignores also the economic cost of the artificial breeding materials themselves.
The intra vaginal progesterone containing devices hitherto used in New Zealand and to a large extent elsewhere are typified by the CIDR(copyright) product of this company depicted hereinafter in FIGS. 1 and 2 being a variable geometry device for vaginal insertion and retention which comprises a structural frame of a metal or appropriate plastics material (eg. nylon) encased in a progesterone impregnated plastics material (eg. silicone) from which the material can leach in the vaginal environment and from which it can be timely withdrawn by appropriate means (eg; a string, tail or a tool) to allow the animal to progress into oestrous shortly after the removal. Reference should be made to New Zealand Patent Specification No. 207341 (U.S. Pat. No. 4,678,463). Hereinafter the aforementioned device will be referred to by its registered trademark CIDR(copyright).
The prior art CIDR(trademark) devices of this company are intra vaginal passive delivery systems to be used in cattle for the control of oestus. Two major uses are in the treatment of anoestrus and synchrony. Other uses include its role in embryo transfer and treatment of cystic ovaries.
Another product available in the market place of this kind is another variable geometry device and such a device is depicted hereinafter in FIG. 3. Such a device is a helical coil capable of being helically tightened and which is retainable in its helical form in the animals vagina. The device includes a withdrawal cord and carries a gelatine capsule which includes oestradiol so that there can be co-administration of the progesterone to be released over a protracted period and the oestradiol which is to be released at a different rate. Such a device includes a progesterone impregnated plastics matrix about a helical spine. Such a device is available from Sanofi Animal Health Limited, PO Box 209, Rhodes Way, Watford, Herts, WD2 4QE, England under its registered trademark PRID(copyright).
Species specific enhancements to better ensure retention of devices abound. See for instance New Zealand Patent Specification No.286984/299060 (PCT/NZ98/00064) that is relevant to pigs.
The aforementioned CIDR(copyright) and PRID(copyright) devices are manufactured in large volumes with the most expensive material being the progesterone active ingredient. Thus small reductions in the progesterone inclusion in such the devices will provide an economic advantage to a producer and to a farmer.
The CIDR(copyright) prior art device of this company has been marketed with a silicone plastics matrix about its spine which contains about 1.9 grams of progesterone (USP) which drops to 1.25 grams still retained in the silicone matrix if the device is withdrawn after only seven days in order to maximise fertility. The same device drops to 1.00 grams of progesterone if it is not withdrawn until after 15 days which is the optimum time for ensuring maximum synchrony.
The PRID(copyright) coil intra vaginal device contains at the outset 1.55 grams of progesterone which reduces down to 0.55 grams after 7 days and down to 0.86 grams after 15 days. The leach rate from the PRID(copyright) product may be affected in part by the inclusion of inorganic materials in the silicone plastics material such as calcium carbonate. The CIDR(copyright) silicone matrix for the progesterone is largely free of any such inclusions.
Our New Zealand Patent Specification No. 286492 (PCT/NZ97/00052 or WO97/40776) discloses a passive delivery device of the CIDR(trademark) type having advantages insofar as reducing the progesterone content is concerned but without any diminution of the delivery. In this respect please see FIG. 13 which is a plot of the plasma progesterone levels for individual ovariectomised cows with this particular intra vaginal passive delivery device (CIDR-B(trademark)) against time. While the individual profiles of individual animals varies having regard to the nature of the animal, eg; its vaginal liquids etc. a general trend is evident, viz, a rapid release upon device insertion to rapidly elevate progesterone plasma levels above 2 ng/mL and to maintain a progesterone plasma level above 2 ng/mL until device removal whereupon the progesterone plasma level rapidly drops.
Therefore a programme of passive delivery utilising the CIDR-B(trademark) with a silicone elastomer containing progesterone moulded over a T shape nylon spine and a CIDRIOL(trademark) capsule which contains oestradiol benzoate and is administered attached to the CIDR-B(trademark) can act to ensure that a fresh follicle is present from the onset of progesterone delivery by the CIDR-B(trademark) device. The length of insertion of the CIDR-B(trademark) device varies but a period as short as five days can now be used. Within 24-48 hours after removal of the device the animal will enter oestrus thereby allowing the predetermined timing of insemination.
Active delivery devices have been used for the delivery of active ingredients into the bodies of mammals (whether for therapeutic purposes with a human or in order to achieve a therapeutic or some other advantageous effect in a non human mammal).
For example, PCT/US89/03705 (published as WO 90/02580) to Brown University Research Foundation discloses an implantable delivery system for biological factors. The disclosure envisages in some instances the use of a preprogrammed micro-processor to control a pumping system responsible, when activated, of actively delivering a desired therapeutic, biologically-active factor, (such as a drug) into the target region into which the implantable device has been inserted.
In September 1996 Plade Holdings Limited launched an active delivery device into the New Zealand market for delivery of active ingredients via the vaginal tract. The device was launched as the SMARTT1(trademark) Intelligent Breeding Device. It included a micro-processor chip programmed to deliver three different active ingredientsxe2x80x94progesterone, oestradiol benzoate and clonprostenol sodium at various times and durations during a 12 day treatment program. Reference should be made to PCT/NZ96/00024 (published as WO 96/29025) of Advanced Animal Technology Limited which relates to the SMARTT1(trademark) product at least in part.
In column 2 lines 52 to 26 WO90/02580 indicates, as an object, the provision of a compact infusion unit which is controlled by electric current supplied by batteries and regulated by means such as an electronic timer, biomedical control means or microprocessor control.
In the SMARTT1(trademark) device each active ingredient is in a liquid form (dissolved in a suitable organic solvent) and is held in a drug reservoir. Each such reservoir is under positive pressure resulting from a spring acting on a plunger or piston. When a solenoid is activated a closure within the solenoid can be opened allowing the liquid to pass from the pressurised reservoir and through a channel running the length of the overall device to be released from its head. By far the bulk of the device (ignoring the variable geometry retention device aspects) are the controller and the pumping mechanisms which occupy greater than 50% of the volume of the device (circuit board, 2AAA batteries, wire, spring, seal, plunger and solid metal components) thus leaving (owing to vaginal tract insertion and retention considerations) the volume of the drug reservoir being limited to about 5 mL.
The present invention in one aspect recognises the desirability, as an alternative to the passive devices, of an active delivery device and in particular although not solely an intra vaginal preferably device useful by way of intra-vaginal insertion of controlling the oestus of animals. Such a device has the prospect of totally delivering its progesterone content.
U.S. Pat. No. 5,318,557 (Elan Medical Technologies Ltd) discloses xe2x80x9csmartxe2x80x9d pill constructions for insertion into a body cavity and having gas generating means to expand one chamber whilst by contraction of another expressing a substance via an outlet thereof. An electrolytic cell is disclosed as a preferred gas generator.
U.S. Pat. No. 5,354,264 of Insutech, Inc. discloses a drug delivery device which utilises gas pressure from free oxygen and hydrogen derived from the electrolysis of water at the electrodes in negatively charged polymeric hydrogels (E-Gel) in the presence of electro-osmosis. The gas pressure forces the infusion of the drugs through appropriate means into the body with the pressure being dependent on the rate of electrolysis which in turn is controlled by an electric current. This means that the rate of drug delivery can be predetermined and precisely controlled under the action of an electronic timer or a biomedical control system.
U.S. Pat. No. 5,354,264 indicates that the system is made possible through the use of a solid water swollen polymeric hydrogel network having negative charges along the polymer back bone or fixed within the polymer network. The system allows electro-conductivity to occur even when using pure water as the electrolyte. Pure water itself does not have electric conductivity compared to the saline solution taught in Gross et al. European Patent Application 0385915. With the negatively charged polymeric hydrogels of Insutech, Inc. electrical current can be conducted along the negative charges of the polymer backbone. The simple phenomena allows water electrolysis around the electrodes to generate hydrogen and oxygen gas only, free of chlorine or other gases which might be present in the case of saline or other solutions containing electrolyte ions.
Two principals governing the flow of water within the solid hydrogel network and the production of gases at the electrodes are discussed. Example 1 of U.S. Pat. No. 5,354,264 discloses a method of preparation of such a hydrogel.
Reference is also drawn to such transdermal and infusion devices as are disclosed in U.S. Pat. No. 4,969,874 (Disetronic Ag), U.S. Pat. No. 5,090,963 (Product Development (ZGS) Ltd), U.S. Pat. No. 5,527,288 (Elan Medical Technologies, Ltd), U.S. Pat. No. 5,062,834 (Product Development (ZGS) Ltd), and U.S. Pat. No. 5,156,591 (S.I. Scientific Innovations Ltd).
We have now determined that with a device such as we have hereafter defined, but without the inwardly directed bladder surrounded dip tube modification, that there can be a passive liquid vehicle release such that after (say) a 7 day insertion period in the vagina of (say) a bovine cow approximately 80% of the initial volume is released.
We believe this has implications on the ability to control the release of the liquid vehicle where the control is to be by the generation of a gas to externally pressurise a bladder of the vehicle.
We have also determined that devices of the kind of the present invention not having such a dip tube do not deliver the vehicle in vivo at the same rate observed in vitro.
We have also determined that the provision of a xe2x80x9cdip tubexe2x80x9d as hereinafter defined is an effective means of providing for a reduction in such passive delivery.
As another example the invention to such devices to dispense liquids into a liquid body such as in reservoirs, fish tank or the like.
Traditionally liquid additions to control the environment of a liquid body (such as that of a fish tank) have been achieved manually by the pouring in of appropriate liquids or by the use of passive release devices such as those including an impregnated matrix from which the desired liquid or liquid bourne active ingredient releases over a period of time.
The present invention is to provide a better control of a release of a desired liquid, (includes emulsions, suspensions, etc.) or to at least provide the public with a useful choice.
In one aspect the present invention consists in a delivery device having a reservoir of variable volume having an outlet through which an included vehicle can be expressed in an liquid form as the volume of the reservoir is actively reduced and wherein there is a tube or equivalent structure (xe2x80x9cdip tubexe2x80x9d) (whether defining said outlet or not) providing a conduit to the outlet from the reservoir of such length and crosssection as to favour active release over passive release.
As used herein the term xe2x80x9coutletxe2x80x9d in respect of the reservoir and the term outlet in respect of the dip tube are preferably one and the same. Constructions are envisaged where the tube may be wholly within a structure defining the reservoir, partly within such a structure and partly outside of such structure or even (at least almost) wholly outside of such structure.
The tube in some forms is at least in part within a collapsible bladder (eg; of a latex or other flexible membrane material). In other forms at least part of a cylinder or the equivalent associated with a piston provides the means to reduce the reservoir volume.
Preferably said dip tube is a plastics tube of circular cross-section less than 1 mm in internal diameter.
Preferably the dip tube is such that the passive vehicle release rate of the device is less than 50% (most preferably less than 20%) of the initial volume of vehicle over any insertion period.
Preferably said outlet at least prior to first use is capped.
Preferably said reservoir can be reduced in volume continuously.
Preferably said reservoir can be reduced in volume intermittently.
Preferably the active reduction of the volume is under the action of either.
i) a gas or gases generated by the application of a controlled or controllable electric current to a water containing matrix contained and/or carried by and/or otherwise associated with the device in such a way as generates free oxygen and free hydrogen (preferably without other gases), or
ii) a gas or gases generated by the electrolysis of water contained in a hydrogel contained and/or carried by the device (preferably a negatively charged hydrogel which enables hydrolysis of the water which does not otherwise contain free ionic species),
Preferably the active reduction is under the action of gas(es) generated by timer and/or microprocessor control of a supply of an electrolysing electric current to a hydrogel.
Preferably the source of electric current is from a battery contained by, carried or otherwise associated with the device.
Preferably said substance is progesterone or a substance having a similar effect.
Preferably said substance is progesterone and the rate of expression enabled, whilst in the vaginal tract of a target mammal, by the content of the bladder, the outlet and the gas generating means is sufficient to first achieve a progesterone plasma level above 2 ng/mL and thereafter maintain a level of at least 2 ng/mL in the mammal for a period of at least 4 days.
Preferably the content of the bladder is from 1 to 60 mL of the delivery liquid.
Preferably said device has a passive delivery rate (over the insertion period) of less than 50% of the initial vehicle volume. Preferably the passive delivery rate is 20% or less.
Preferably, but for the dip tube, the passive delivery rate would be over 20% (and indeed possibly over 50%) of the initial vehicle volume.
Preferably there is sufficient hydrogel to enable an active delivery of greater than 50% (and preferably at least 80%) of the initial vehicle volume of the insertion period.
Preferably the insertion period is at least 4 days.
The device may have a plurality of delivery mechanisms and each or some may be active delivery mechanisms controlled by gas pressure and may include a bladder as opposed to a piston expression.
Preferably said device has a removable seal or cap of said outlet (i) capable of being removed prior to intra vaginal insertion, (ii) which dissolves in the vaginal tract after insertion and/or (iii) which is rupturable under the pressure of the delivery liquid to be released after sufficient gas has been generated by said gas generating means after switch means energising of the circuit.
Preferably said device includes a plurality of such reservoirs of variable geometry each preferably each separately controlled insofar as the expression therefrom of its content is concerned.
Preferably said device is an intra-vaginal device.
Preferably the intra vaginal device is of a variable geometry construction which assists insertion and retention of the device in the vagina of a target species.
Preferably said device includes a plurality of such reservoirs of variable geometry.
Preferably each or several of said reservoirs is separately controlled insofar as the expression therefrom of its content is concerned.
Preferably the expression of progesterone or progesterone containing liquid is substantially continuous and preferably without being pulsile in nature.
Preferably said device includes a number of reservoirs of variable geometry and the substance to the delivered from at least one of the reservoirs of variable geometry is a progesterone.
Preferably the substance to be delivered from at least one other reservoir of variable geometry (whether solid, powder, in a liquid form, or otherwise) are active ingredients such as those hitherto discussed useful in conjunction with progesterone in controlling the synchrony of oestrus in mammals.
Another aspect of the prevent invention consists in a delivery device capable of expressing a liquid vehicle from the outlet of a reservoir, said device having timer and/or microprocessor means, a power source and appropriate circuitry, electrodes and electrolyte matrix to be able to generate a gas from the electrolyte matrix so as to reduce the volume of the reservoir to cause active expression of the vehicle therefrom, there being a tube or equivalent structure (xe2x80x9cdip tubexe2x80x9d) (whether defining said outlet or not) providing a conduit to the outlet from the reservoir of such length and cross section as to favour active release of the vehicle from the reservoir over passive release of the vehicle from the reservoir.
In still a further aspect the present invention consists in a delivery device capable of expressing a liquid vehicle from the outlet of a reservoir, said device having timer and/or microprocessor means, a power source and appropriate circuitry, electrodes and electrolyte matrix to be able to generate a gas from the electrolyte matrix so as to reduce the volume of the reservoir to cause active expression of the vehicle therefrom, there bring a tube or equivalent structure (xe2x80x9cdip tubexe2x80x9d) (whether defining said outlet or not) providing a conduit to the outlet.
Preferably the conduit by capillary or other resistance to passive flow of the vehicle from the reservoir (whether whilst there is any active expression or not) is such as to reduce any such passive egress of the vehicle.
In another aspect the present invention consists in a delivery device,
wherein said body has
a chamber to an outlet,
a bladder within said chamber sealed about said outlet to said body so as to be capable of delivering its contents via said outlet upon the application of gas pressure external of said bladder to the bladder, said bladder containing at least 1 mL (preferably at least 5 mL) of said substance in a liquid delivery form, a tube or equivalent structure (xe2x80x9cdip tubexe2x80x9d) providing a conduit to the outlet from within the bladder (preferably provided to affect the passive leakage rate of the delivery device),
and
controlled or controllable gas generating means to generate a gas within said body so as to apply gas pressure within said chamber to the exterior of said bladder,
and wherein the gas generating means include
a hydrogel having electrolysis electrodes,
a battery powered circuit capable of applying a controlled or set current to said electrolysis electrodes so as to generate gas from the hydrogel which will have a pressurising effect on the exterior of said bladder,
switch means to allow energising of the circuit.
Preferably said xe2x80x9coutletxe2x80x9d is as previously defined.
Preferably said device is an intra vaginal device having an elongate body structure coupled to or having resilient means of variable geometry to facilitate in a target mammal vaginal tract insertion, to facilitate vaginal tract retention and to allow vaginal tract withdrawal, when the elongate axis of said body structure is substantially aligned to axis of the vaginal tract.
Preferably said substance is progesterone or a substance having a similar effect.
Preferably said substance is progesterone and the rate of expression enabled, whilst in the vaginal tract of a target mammal, by the content of the bladder, the outlet and the gas generating means is sufficient to first achieve a progesterone plasma level above 2 ng/mL and thereafter maintain a level of at least 2 ng/mL in the mammal for a period of at least 4 days.
Preferably said dip tube is a plastics tube of circular cross-section less than 1 mm in internal diameter.
Preferably said dip tube extends longitudinally of said body structure within said bladder.
Preferably the content of the bladder is from 1 to 60 mL of the delivery liquid.
Preferably said device has a passive delivery rate (over the insertion period) of less than 50% of the initial vehicle volume. Preferably the passive delivery rate is 20% or less.
Preferably, but for the dip tube, the passive delivery rate would be over 20% (and indeed possibly over 50%) of the initial vehicle volume.
Preferably there is sufficient hydrogel to enable an active delivery of greater than 50% (and preferably at least 80%) of the initial vehicle volume of the insertion period.
Preferably the insertion period is at least 4 days.
The device may have a plurality of delivery mechanisms and each or some may be active delivery mechanisms controlled by gas pressure and may include a bladder as opposed to a piston expression.
Preferably said device has a removable seal or cap of said outlet (i) capable of being removed prior to intra vaginal insertion, (ii) which dissolves in the vaginal tract after insertion and/or (iii) which is rupturable under the pressure of the delivery liquid to be released after sufficient gas has been generated by said gas generating means after switch means energising of the circuit.
Preferably said switch means is a manually actuable switch externally accessible prior to the insertion of the device in the vaginal tract of a target mammal.
Preferably said device includes a timer or a logic means which controls the provision of current to the electrolysis electrodes after actuation of said switch means.
Preferably said elongate body structure defines a second chamber in communication with said first chamber and said hydrogel is located in that second chamber.
Preferably said second chamber or an additional chamber locates the battery of said battery powered circuit.
Preferably said elongate body structure includes means remote from the outlet which facilitates the withdrawal of the device from the vaginal tract of a target mammal.
In another aspect the present invention consists in the related methods and use.
In another aspect the present invention consists in a device for releasing a liquid or fluid vehicle [eg; into a liquid body (whether from above or below the surface of the liquid body)], said device comprising
a housing defining a cavity,
a liquid or fluid (hereafter xe2x80x9cliquidxe2x80x9d) containing bladder located in said housing, said bladder having means providing an outlet capable of discharging its liquid out of said housing,
gas generating means disposed within said housing to generate at least partly in said housing gas to impinge upon the exterior of said bladder, and
control circuit means to cause a controlled generation of gas from said gas generating means and thus the controlled expression of liquid from said bladder.
Preferably said gas generating means and/or said electrical circuit means comprises a system as disclosed in U.S. Pat. No. 5,354,264 of Insutech Inc and/or U.S. Pat. No. 5,318,557 of Elan Medical Technologies Ltd i.e. an electrolytic cell having electrodes.
Preferably the electrical circuit means to the electrode(s) of said gas generating means, a source of current for said electrical circuit means (e.g. batteries), and means for activating the circuit and thus the energising of said electrode(s).
Preferably said means to control includes a switch and/or programmed logic means.
Preferably said device includes a removable or rupturable seal of said outlet.
Preferably said device is of a kind of sufficient mass so as to be submersible in the liquid into which the liquid of the bladder is to be discharged.
Preferably the liquid of the bladder (whether because of its viscosity, resilience of the outlet or any conduit thereto, size of the outlet or any conduit thereto or otherwise) unless actively expressed by further gas generation leaks (if at all) out of said outlet at a rate below that desired.
In other forms the device is adapted to discharge liquid onto the surface of the liquid.
In some forms of the present invention the device is adapted to discharge liquid from the outlet, the outlet being at an end of a tube, conduit or other passageway leading internally into the bladder.
Preferably said tube is in the form of a dip tube which is adapted to discharge liquid upwardly from within the bladder.
Preferably the device is substantially as hereinafter described with reference to any one or more of the accompanying drawings.
In a further aspect the present invention consists in a method of continuously or incrementally releasing a liquid vehicle, said method involving the use operatively of a device in accordance with the present invention.
Preferably said use involves switching the device on prior to its association operatively with the body of liquid into which or onto which it is to discharge.
Preferably said body of liquid into which or onto which it is to discharge is a fish tank.